Project acronym AF and MSOGR
Project Automorphic Forms and Moduli Spaces of Galois Representations
Researcher (PI) Toby Gee
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Call Details Starting Grant (StG), PE1, ERC-2012-StG_20111012
Summary I propose to establish a research group to develop completely new tools in order to solve three important problems on the relationships between automorphic forms and Galois representations, which lie at the heart of the Langlands program. The first is to prove Serre’s conjecture for real quadratic fields. I will use automorphic induction to transfer the problem to U(4) over the rational numbers, where I will use automorphy lifting theorems and results on the weight part of Serre's conjecture that I established in my earlier work to reduce the problem to proving results in small weight and level. I will prove these base cases via integral p-adic Hodge theory and discriminant bounds.
The second is to develop a geometric theory of moduli spaces of mod p and p-adic Galois representations, and to use it to establish the Breuil–Mézard conjecture in arbitrary dimension, by reinterpreting the conjecture in geometric terms. This will transform the subject by building the first connections between the p-adic Langlands program and the geometric Langlands program, providing an entirely new world of techniques for number theorists. As a consequence of the Breuil-Mézard conjecture, I will be able to deduce far stronger automorphy lifting theorems (in arbitrary dimension) than those currently available.
The third is to completely determine the reduction mod p of certain two-dimensional crystalline representations, and as an application prove a strengthened version of the Gouvêa–Mazur conjecture. I will do this by means of explicit computations with the p-adic local Langlands correspondence for GL_2(Q_p), as well as by improving existing arguments which prove multiplicity one theorems via automorphy lifting theorems. This work will show that the existence of counterexamples to the Gouvêa-Mazur conjecture is due to a purely local phenomenon, and that when this local obstruction vanishes, far stronger conjectures of Buzzard on the slopes of the U_p operator hold.
Summary
I propose to establish a research group to develop completely new tools in order to solve three important problems on the relationships between automorphic forms and Galois representations, which lie at the heart of the Langlands program. The first is to prove Serre’s conjecture for real quadratic fields. I will use automorphic induction to transfer the problem to U(4) over the rational numbers, where I will use automorphy lifting theorems and results on the weight part of Serre's conjecture that I established in my earlier work to reduce the problem to proving results in small weight and level. I will prove these base cases via integral p-adic Hodge theory and discriminant bounds.
The second is to develop a geometric theory of moduli spaces of mod p and p-adic Galois representations, and to use it to establish the Breuil–Mézard conjecture in arbitrary dimension, by reinterpreting the conjecture in geometric terms. This will transform the subject by building the first connections between the p-adic Langlands program and the geometric Langlands program, providing an entirely new world of techniques for number theorists. As a consequence of the Breuil-Mézard conjecture, I will be able to deduce far stronger automorphy lifting theorems (in arbitrary dimension) than those currently available.
The third is to completely determine the reduction mod p of certain two-dimensional crystalline representations, and as an application prove a strengthened version of the Gouvêa–Mazur conjecture. I will do this by means of explicit computations with the p-adic local Langlands correspondence for GL_2(Q_p), as well as by improving existing arguments which prove multiplicity one theorems via automorphy lifting theorems. This work will show that the existence of counterexamples to the Gouvêa-Mazur conjecture is due to a purely local phenomenon, and that when this local obstruction vanishes, far stronger conjectures of Buzzard on the slopes of the U_p operator hold.
Max ERC Funding
1 131 339 €
Duration
Start date: 2012-10-01, End date: 2017-09-30
Project acronym APGRAPH
Project Asymptotic Graph Properties
Researcher (PI) Deryk Osthus
Host Institution (HI) THE UNIVERSITY OF BIRMINGHAM
Call Details Starting Grant (StG), PE1, ERC-2012-StG_20111012
Summary Many parts of Graph Theory have witnessed a huge growth over the last years, partly because of their relation to Theoretical Computer Science and Statistical Physics. These connections arise because graphs can be used to model many diverse structures.
The focus of this proposal is on asymptotic results, i.e. the graphs under consideration are large. This often unveils patterns and connections which remain obscure when considering only small graphs.
It also allows for the use of powerful techniques such as probabilistic arguments, which have led to spectacular new developments. In particular, my aim is to make decisive progress on central problems in the following 4 areas:
(1) Factorizations: Factorizations of graphs can be viewed as partitions of the edges of a graph into simple regular structures. They have a rich history and arise in many different settings, such as edge-colouring problems, decomposition problems and in information theory. They also have applications to finding good tours for the famous Travelling salesman problem.
(2) Hamilton cycles: A Hamilton cycle is a cycle which contains all the vertices of the graph. One of the most fundamental problems in Graph Theory/Theoretical Computer Science is to find conditions which guarantee the existence of a Hamilton cycle in a graph.
(3) Embeddings of graphs: This is a natural (but difficult) continuation of the previous question where the aim is to embed more general structures than Hamilton cycles - there has been exciting progress here in recent years which has opened up new avenues.
(4) Resilience of graphs: In many cases, it is important to know whether a graph `strongly’ possesses some property, i.e. one cannot destroy the property by changing a few edges. The systematic study of this notion is a new and rapidly growing area.
I have developed new methods for deep and long-standing problems in these areas which will certainly lead to further applications elsewhere.
Summary
Many parts of Graph Theory have witnessed a huge growth over the last years, partly because of their relation to Theoretical Computer Science and Statistical Physics. These connections arise because graphs can be used to model many diverse structures.
The focus of this proposal is on asymptotic results, i.e. the graphs under consideration are large. This often unveils patterns and connections which remain obscure when considering only small graphs.
It also allows for the use of powerful techniques such as probabilistic arguments, which have led to spectacular new developments. In particular, my aim is to make decisive progress on central problems in the following 4 areas:
(1) Factorizations: Factorizations of graphs can be viewed as partitions of the edges of a graph into simple regular structures. They have a rich history and arise in many different settings, such as edge-colouring problems, decomposition problems and in information theory. They also have applications to finding good tours for the famous Travelling salesman problem.
(2) Hamilton cycles: A Hamilton cycle is a cycle which contains all the vertices of the graph. One of the most fundamental problems in Graph Theory/Theoretical Computer Science is to find conditions which guarantee the existence of a Hamilton cycle in a graph.
(3) Embeddings of graphs: This is a natural (but difficult) continuation of the previous question where the aim is to embed more general structures than Hamilton cycles - there has been exciting progress here in recent years which has opened up new avenues.
(4) Resilience of graphs: In many cases, it is important to know whether a graph `strongly’ possesses some property, i.e. one cannot destroy the property by changing a few edges. The systematic study of this notion is a new and rapidly growing area.
I have developed new methods for deep and long-standing problems in these areas which will certainly lead to further applications elsewhere.
Max ERC Funding
818 414 €
Duration
Start date: 2012-12-01, End date: 2018-11-30
Project acronym BALDWINIAN_BEETLES
Project "The origin of the fittest: canalization, plasticity and selection as a consequence of provisioning during development"
Researcher (PI) Rebecca Kilner
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Starting Grant (StG), LS8, ERC-2012-StG_20111109
Summary "A major outstanding challenge for evolutionary biology is to explain how novel adaptations arise. We propose to test whether developmental plasticity initiates evolutionary change in morphological, behavioural and social traits, using laboratory experiments, fieldwork and comparative analyses.
Using burying beetles Nicrophorus spp as our model experimental system, we shall:
1) Test whether variation in parental provisioning during development induces correlated phenotypic change in adult body size and a suite of life history traits; whether these phenotypic changes can be genetically accommodated under experimental evolution (the Baldwin Effect); and whether changes induced by experimental evolution mimic natural variation in adult body size and life history strategy among Nicrophorus species;
2) Test whether parental provisioning has a canalizing effect on the developmental environment, potentially storing up cryptic genetic variation which might then be released as random new phenotypes, if offspring are exposed to a new developmental environment;
3) Investigate whether developmental trade-offs, induced by under-provisioning from parents, provide the first step towards the evolution of a novel interspecific mutualism. Is a second species recruited in adulthood to carry out the function of a structure that was under-nourished during development?
4) Using comparative analyses of data from the literature on insects, frogs, birds and mammals, we shall test whether the evolution of parental provisioning in a given lineage is positively correlated with the number of species in the lineage.
Our proposal is original in focusing on developmental plasticity induced by variation in parental provisioning. Given the diverse and numerous species that provision their young, including several whose genomes have now been sequenced, this potentially opens up a rich new area for future work on the developmental mechanisms underlying evolutionary innovations."
Summary
"A major outstanding challenge for evolutionary biology is to explain how novel adaptations arise. We propose to test whether developmental plasticity initiates evolutionary change in morphological, behavioural and social traits, using laboratory experiments, fieldwork and comparative analyses.
Using burying beetles Nicrophorus spp as our model experimental system, we shall:
1) Test whether variation in parental provisioning during development induces correlated phenotypic change in adult body size and a suite of life history traits; whether these phenotypic changes can be genetically accommodated under experimental evolution (the Baldwin Effect); and whether changes induced by experimental evolution mimic natural variation in adult body size and life history strategy among Nicrophorus species;
2) Test whether parental provisioning has a canalizing effect on the developmental environment, potentially storing up cryptic genetic variation which might then be released as random new phenotypes, if offspring are exposed to a new developmental environment;
3) Investigate whether developmental trade-offs, induced by under-provisioning from parents, provide the first step towards the evolution of a novel interspecific mutualism. Is a second species recruited in adulthood to carry out the function of a structure that was under-nourished during development?
4) Using comparative analyses of data from the literature on insects, frogs, birds and mammals, we shall test whether the evolution of parental provisioning in a given lineage is positively correlated with the number of species in the lineage.
Our proposal is original in focusing on developmental plasticity induced by variation in parental provisioning. Given the diverse and numerous species that provision their young, including several whose genomes have now been sequenced, this potentially opens up a rich new area for future work on the developmental mechanisms underlying evolutionary innovations."
Max ERC Funding
1 499 914 €
Duration
Start date: 2012-11-01, End date: 2017-10-31
Project acronym BP-CarDiO
Project Investigating the therapeutic potential of manipulating the IGF-IGFBP1 axis in the prevention and treatment of cardiovascular disease, diabetes and obesity
Researcher (PI) Stephen Bentley Wheatcroft
Host Institution (HI) UNIVERSITY OF LEEDS
Call Details Starting Grant (StG), LS4, ERC-2012-StG_20111109
Summary More than 30 million people are living with diabetes in the EU, with a prevalence expected to grow to over 10% of the adult population by the year 2030. Type 2 diabetes is a major cause of cardiovascular disease related death and disability, substantially increasing the risk of myocardial infarction, stroke and peripheral arterial disease. Recent landmark trials, showing that intensive glucose control does not improve cardiovascular outcomes and may increase mortality in some circumstances, provide a compelling rationale for intense research aimed at developing novel therapeutic strategies. Type 2 diabetes is underpinned by resistance to the effects of insulin, which I have shown in endothelial cells causes reduced bioavailability of the anti-atherosclerotic molecule nitric oxide and leads to accelerated atherosclerosis. The cellular effects of insulin are mirrored by insulin-like growth factor factor-1, the bioavailability of which at its receptor is in turn is regulated by a family of high affinity binding proteins (IGFBP). Epidemiological studies demonstrate and inverse association between one of these binding proteins, IGFBP1, and diabetes-related cardiovascular risk. I have recently demonstrated that IGFBP1 when expressed in mice can ameliorate insulin resistance, obesity and atherosclerosis. In endothelial cells, I showed that IGFBP1 upregulates the production of nitric oxide indepenedently of IGF. These findings suggest that IGFBP1 may be a ‘protective’ endogenous protein and that increasing circulating levels may be a therapeutic strategy to prevent development of diabetes and cardiovascular disease. In this proposal I will address this hypothesis by employing state of the art studies in cells and novel gene modified mice to unravel the molecular basis of the protective effects of IGFBP1 and to investigate the possibility of exploiting the IGF-IGFBP axis to prevent cardiovascular disease in the setting of diabetes and obesity.
Summary
More than 30 million people are living with diabetes in the EU, with a prevalence expected to grow to over 10% of the adult population by the year 2030. Type 2 diabetes is a major cause of cardiovascular disease related death and disability, substantially increasing the risk of myocardial infarction, stroke and peripheral arterial disease. Recent landmark trials, showing that intensive glucose control does not improve cardiovascular outcomes and may increase mortality in some circumstances, provide a compelling rationale for intense research aimed at developing novel therapeutic strategies. Type 2 diabetes is underpinned by resistance to the effects of insulin, which I have shown in endothelial cells causes reduced bioavailability of the anti-atherosclerotic molecule nitric oxide and leads to accelerated atherosclerosis. The cellular effects of insulin are mirrored by insulin-like growth factor factor-1, the bioavailability of which at its receptor is in turn is regulated by a family of high affinity binding proteins (IGFBP). Epidemiological studies demonstrate and inverse association between one of these binding proteins, IGFBP1, and diabetes-related cardiovascular risk. I have recently demonstrated that IGFBP1 when expressed in mice can ameliorate insulin resistance, obesity and atherosclerosis. In endothelial cells, I showed that IGFBP1 upregulates the production of nitric oxide indepenedently of IGF. These findings suggest that IGFBP1 may be a ‘protective’ endogenous protein and that increasing circulating levels may be a therapeutic strategy to prevent development of diabetes and cardiovascular disease. In this proposal I will address this hypothesis by employing state of the art studies in cells and novel gene modified mice to unravel the molecular basis of the protective effects of IGFBP1 and to investigate the possibility of exploiting the IGF-IGFBP axis to prevent cardiovascular disease in the setting of diabetes and obesity.
Max ERC Funding
1 493 543 €
Duration
Start date: 2013-01-01, End date: 2017-12-31
Project acronym BrainGutTalk
Project Brain-gut interactions in Drosophila melanogaster
Researcher (PI) Irene Miguel-Aliaga
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Call Details Starting Grant (StG), LS4, ERC-2012-StG_20111109
Summary The gastrointestinal tract is emerging as a key regulator of appetite and metabolism, but studies aimed at identifying the signals involved are faced with daunting neuroanatomical complexity: there are as many as 500 million neurons in the human gut. Drosophila should provide a simple and genetically amenable alternative, but both its autonomic nervous system and the signalling significance of its digestive tract have remained largely unexplored. My research programme will characterize the signals and neurons mediating the interaction between the nervous and digestive systems, and will establish their significance both in the maintenance of metabolic homeostasis and in response to nutritional challenges. To achieve these goals, we will capitalize on a multi-disciplinary approach that combines the genetic manipulation of defined neuronal lineages, a cell-biological approach to the study of enterocyte metabolism, and our recently developed physiological and behavioural readouts. Our work will provide new insights into the signals and mechanisms modulating internal metabolism and food intake: processes which, when deregulated, contribute to increasingly prevalent conditions such as diabetes, metabolic syndrome and obesity. Our recent finding of conserved mechanisms of autonomic control in the fruit fly makes us confident that the signals we identify will be relevant to mammalian systems.
Summary
The gastrointestinal tract is emerging as a key regulator of appetite and metabolism, but studies aimed at identifying the signals involved are faced with daunting neuroanatomical complexity: there are as many as 500 million neurons in the human gut. Drosophila should provide a simple and genetically amenable alternative, but both its autonomic nervous system and the signalling significance of its digestive tract have remained largely unexplored. My research programme will characterize the signals and neurons mediating the interaction between the nervous and digestive systems, and will establish their significance both in the maintenance of metabolic homeostasis and in response to nutritional challenges. To achieve these goals, we will capitalize on a multi-disciplinary approach that combines the genetic manipulation of defined neuronal lineages, a cell-biological approach to the study of enterocyte metabolism, and our recently developed physiological and behavioural readouts. Our work will provide new insights into the signals and mechanisms modulating internal metabolism and food intake: processes which, when deregulated, contribute to increasingly prevalent conditions such as diabetes, metabolic syndrome and obesity. Our recent finding of conserved mechanisms of autonomic control in the fruit fly makes us confident that the signals we identify will be relevant to mammalian systems.
Max ERC Funding
1 499 740 €
Duration
Start date: 2013-02-01, End date: 2018-01-31
Project acronym CANCERPHAGY
Project Autophagy as a cancer treatment
Researcher (PI) Ivana Bjedov
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Call Details Starting Grant (StG), LS4, ERC-2012-StG_20111109
Summary Cancer is one of the most prevalent human killer diseases. Autophagy, a lysosome-mediated process that degrades cellular components and damaged organelles, has recently emerged as an important player in cancer. Indeed, autophagy inhibition promotes cancer initiation through generation of genomic instability and inflammation, whereas in contrast, autophagy activation is often required to sustain growth of advanced solid tumours in a nutrient-deprived hypoxic environment. Recent findings firmly demonstrate that modulating autophagy can potentially be exploited to suppress tumours and to avoid resistance in anti-cancer therapy. However, the interplay between cancer and autophagy is complex, and further in-depth investigation is urgently required. Therefore I propose to use the well-described cancer models in Drosophila, together with the autophagy mutants that I have developed, firstly to test how an autophagy-proficient/deficient host environment alters growth and dissemination of allografted tumours. Secondly, I will examine how modulation of autophagy within the tumour can impact on its growth. In order to alter independently tumour induction with autophagy inhibition/activation, I will make use of the two inducible expression systems currently only available for Drosophila. These experiments will be accompanied by detailed analysis of mitochondrial status, as well as protein damage and DNA lesions, which will shed light on the intricate mechanisms whereby autophagy affects cancer and will help indicate optimal time points for further analysis of the tumours by in-depth transcriptional, proteomic and metabolomic profiling. Collectively, this project proposal is designed to rapidly test various hypotheses for cancer prevention and treatment, to provide valuable insights for further validation in higher organisms, and to identify new potential drug targets for cancer research.
Summary
Cancer is one of the most prevalent human killer diseases. Autophagy, a lysosome-mediated process that degrades cellular components and damaged organelles, has recently emerged as an important player in cancer. Indeed, autophagy inhibition promotes cancer initiation through generation of genomic instability and inflammation, whereas in contrast, autophagy activation is often required to sustain growth of advanced solid tumours in a nutrient-deprived hypoxic environment. Recent findings firmly demonstrate that modulating autophagy can potentially be exploited to suppress tumours and to avoid resistance in anti-cancer therapy. However, the interplay between cancer and autophagy is complex, and further in-depth investigation is urgently required. Therefore I propose to use the well-described cancer models in Drosophila, together with the autophagy mutants that I have developed, firstly to test how an autophagy-proficient/deficient host environment alters growth and dissemination of allografted tumours. Secondly, I will examine how modulation of autophagy within the tumour can impact on its growth. In order to alter independently tumour induction with autophagy inhibition/activation, I will make use of the two inducible expression systems currently only available for Drosophila. These experiments will be accompanied by detailed analysis of mitochondrial status, as well as protein damage and DNA lesions, which will shed light on the intricate mechanisms whereby autophagy affects cancer and will help indicate optimal time points for further analysis of the tumours by in-depth transcriptional, proteomic and metabolomic profiling. Collectively, this project proposal is designed to rapidly test various hypotheses for cancer prevention and treatment, to provide valuable insights for further validation in higher organisms, and to identify new potential drug targets for cancer research.
Max ERC Funding
1 453 219 €
Duration
Start date: 2012-10-01, End date: 2018-09-30
Project acronym COEVOCON
Project Coevolution of bacteria and conjugative plasmids
Researcher (PI) Michael Brockhurst
Host Institution (HI) THE UNIVERSITY OF SHEFFIELD
Call Details Starting Grant (StG), LS8, ERC-2012-StG_20111109
Summary Horizontal gene transfer (HGT) is a fundamental process of bacterial evolution, accelerating adaptation to novel environments and providing access to new ecological niches. However, two of the three mechanisms of HGT, transduction and conjugation, both rely on semi-autonomous vectors (lysogenic phages and conjugative plasmids, respectively), creating the potential for coadaptation between microbe and vector. I here focus on conjugative plasmids. These encode their own replication and transfer, and as such are capable of pursuing their own fitness interests, which need not be aligned with those of their bacterial host. My thesis is that bacterial adaptation by conjugation must therefore be viewed as a co-evolutionary, rather than simply an evolutionary process as achieved to date. In this proposal I take an experimental evolution approach to derive an empirically founded understanding of bacteria-plasmid coevolutionary processes. In particular, I focus on the effects (on the pattern and process of bacteria-plasmid coevolution) of ecological variables identified in population models as crucial to the persistence of conjugative plasmids: environmental heterogeneity, spatial structure, and between-species transfer. Drawing on coevolutionary theory, I highlight that the ecological conditions expected to favour plasmid persistence may often drive the breakdown of bacteria-plasmid coadaptation. Additionally, I will determine the consequences of bacteria-plasmid coevolution for the structuring of microbial communities.
Summary
Horizontal gene transfer (HGT) is a fundamental process of bacterial evolution, accelerating adaptation to novel environments and providing access to new ecological niches. However, two of the three mechanisms of HGT, transduction and conjugation, both rely on semi-autonomous vectors (lysogenic phages and conjugative plasmids, respectively), creating the potential for coadaptation between microbe and vector. I here focus on conjugative plasmids. These encode their own replication and transfer, and as such are capable of pursuing their own fitness interests, which need not be aligned with those of their bacterial host. My thesis is that bacterial adaptation by conjugation must therefore be viewed as a co-evolutionary, rather than simply an evolutionary process as achieved to date. In this proposal I take an experimental evolution approach to derive an empirically founded understanding of bacteria-plasmid coevolutionary processes. In particular, I focus on the effects (on the pattern and process of bacteria-plasmid coevolution) of ecological variables identified in population models as crucial to the persistence of conjugative plasmids: environmental heterogeneity, spatial structure, and between-species transfer. Drawing on coevolutionary theory, I highlight that the ecological conditions expected to favour plasmid persistence may often drive the breakdown of bacteria-plasmid coadaptation. Additionally, I will determine the consequences of bacteria-plasmid coevolution for the structuring of microbial communities.
Max ERC Funding
1 233 610 €
Duration
Start date: 2013-02-01, End date: 2018-01-31
Project acronym EC
Project Extremal Combinatorics
Researcher (PI) Oleg Pikhurko
Host Institution (HI) THE UNIVERSITY OF WARWICK
Call Details Starting Grant (StG), PE1, ERC-2012-StG_20111012
Summary A typical problem of Extremal Combinatorics is to maximise or minimise a certain parameter given some combinatorial restrictions. This area experienced a remarkable growth in the last few decades, having a wide range of applications that include results in number theory, algebra, geometry, logic, information theory, and theoretical computer science. There are also many practical fields that were greatly influenced by ideas from Extremal Combinatorics such as, for example, analysis of large networks, ranking of web-pages, or shotgun cloning of DNA fragments.
The Principal Investigator (PI for short) will work on a number of extremal problems, with the main directions being the Tur\'an function (maximising the size of a hypergraph without some fixed forbidden subgraphs), the Rademacher-Tur\'an problem (minimising the density of F-subgraphs given the edge density), and Ramsey numbers (quantitative bounds on the maximum size of a monochromatic substructure that exists for every colouring). These are fundamental and general questions that go back at least as far as the 1940s but remain wide open despite decades of active attempts. During attacks on these notoriously difficult problems, mathematicians developed a number of powerful general methods. PI will work on extending and sharpening these techniques as well as on finding ways of applying the recently introduced concepts of (hyper)graph limits and flag algebras to concrete extremal problems. Since these concepts deal with some approximation to the studied problem, one important aspect of the project is to develop methods for obtaining exact results from asymptotic calculations (for example, via the stability approach).
The support by means of a 5-year research grant will enable PI to consolidate his research and build a group in Extremal Combinatorics.
Summary
A typical problem of Extremal Combinatorics is to maximise or minimise a certain parameter given some combinatorial restrictions. This area experienced a remarkable growth in the last few decades, having a wide range of applications that include results in number theory, algebra, geometry, logic, information theory, and theoretical computer science. There are also many practical fields that were greatly influenced by ideas from Extremal Combinatorics such as, for example, analysis of large networks, ranking of web-pages, or shotgun cloning of DNA fragments.
The Principal Investigator (PI for short) will work on a number of extremal problems, with the main directions being the Tur\'an function (maximising the size of a hypergraph without some fixed forbidden subgraphs), the Rademacher-Tur\'an problem (minimising the density of F-subgraphs given the edge density), and Ramsey numbers (quantitative bounds on the maximum size of a monochromatic substructure that exists for every colouring). These are fundamental and general questions that go back at least as far as the 1940s but remain wide open despite decades of active attempts. During attacks on these notoriously difficult problems, mathematicians developed a number of powerful general methods. PI will work on extending and sharpening these techniques as well as on finding ways of applying the recently introduced concepts of (hyper)graph limits and flag algebras to concrete extremal problems. Since these concepts deal with some approximation to the studied problem, one important aspect of the project is to develop methods for obtaining exact results from asymptotic calculations (for example, via the stability approach).
The support by means of a 5-year research grant will enable PI to consolidate his research and build a group in Extremal Combinatorics.
Max ERC Funding
1 129 919 €
Duration
Start date: 2012-10-01, End date: 2018-07-31
Project acronym EVOGENO
Project Dissecting the genetic basis of divergent and convergent evolution: From individuals to species radiations
Researcher (PI) Stephen James Rossiter
Host Institution (HI) QUEEN MARY UNIVERSITY OF LONDON
Call Details Starting Grant (StG), LS8, ERC-2012-StG_20111109
Summary Advances in genomics offer new opportunities for identifying loci that behave unusually against a background of neutral variation. Detecting divergent sites among related individuals and taxa can shed light on the process of adaptive divergence, from non-random mating to the establishment of reproductive barriers. Conversely, identifying convergent sites among unrelated taxa can offer insights into deeper level ecological radiations. This project will study genes underpinning evolutionary divergence at several stages. Discovering genome-wide ‘gene outliers’ presents enormous challenges. I argue these can be overcome by combining and applying phylogenetic and evolutionary analyses with deep sequencing to exceptional study systems. Among mammals, bats are unique in having independently evolved laryngeal echolocation and nectarivory, both implicated in their unparalleled adaptive radiation. We will (i) use a novel phylogenomic approach to identify genes under convergent and divergent selection associated with acoustic and dietary diversification. (ii) We will then discover additional loci implicated in diverging incipient sympatric taxa that have undergone recent dramatic call frequency shifts. (iii) We will identify genome-wide loci that show anomalous divergence and non-random combinations between faithfully breeding pairs of bats in a population where outbreeding increases fitness. These complementary studies will produce a database of candidate loci implicated in ecological divergence. We will then verify and synthesize our results by screening the genes in a taxonomically wider range of species. We hope to provide a comprehensive assessment of the relative numbers and importance of different types of loci in multiple stages of evolutionary divergence in a mammalian system. As such these results will significantly extend the current frontier of our knowledge about how new taxa form.
Summary
Advances in genomics offer new opportunities for identifying loci that behave unusually against a background of neutral variation. Detecting divergent sites among related individuals and taxa can shed light on the process of adaptive divergence, from non-random mating to the establishment of reproductive barriers. Conversely, identifying convergent sites among unrelated taxa can offer insights into deeper level ecological radiations. This project will study genes underpinning evolutionary divergence at several stages. Discovering genome-wide ‘gene outliers’ presents enormous challenges. I argue these can be overcome by combining and applying phylogenetic and evolutionary analyses with deep sequencing to exceptional study systems. Among mammals, bats are unique in having independently evolved laryngeal echolocation and nectarivory, both implicated in their unparalleled adaptive radiation. We will (i) use a novel phylogenomic approach to identify genes under convergent and divergent selection associated with acoustic and dietary diversification. (ii) We will then discover additional loci implicated in diverging incipient sympatric taxa that have undergone recent dramatic call frequency shifts. (iii) We will identify genome-wide loci that show anomalous divergence and non-random combinations between faithfully breeding pairs of bats in a population where outbreeding increases fitness. These complementary studies will produce a database of candidate loci implicated in ecological divergence. We will then verify and synthesize our results by screening the genes in a taxonomically wider range of species. We hope to provide a comprehensive assessment of the relative numbers and importance of different types of loci in multiple stages of evolutionary divergence in a mammalian system. As such these results will significantly extend the current frontier of our knowledge about how new taxa form.
Max ERC Funding
1 499 914 €
Duration
Start date: 2013-02-01, End date: 2019-01-31
Project acronym FANTAST
Project Frontiers of Analytic Number Theory And Selected Topics
Researcher (PI) Timothy Daniel Browning
Host Institution (HI) UNIVERSITY OF BRISTOL
Call Details Starting Grant (StG), PE1, ERC-2012-StG_20111012
Summary "This proposal sits at the interface of analytic number theory and selected topics, viewed through the prism of Diophantine equations defining higher-dimensional algebraic varieties. A core part of the proposal involves using analytic methods (such as complex analysis, Fourier analysis and additive combinatorics) to tackle a range of problems about Diophantine equations. These include such
basic questions as precisely when families of equations admit integer or rational solutions and, furthermore, how ``dense'' these solutions are when they exist. In the reverse direction, a significant component of the proposal is dedicated to established problems in number theory (such as stable cohomology of moduli spaces and uniform spectral gaps for arithmetic lattices) which can be tackled via the successful analysis of intermediary Diophantine equations."
Summary
"This proposal sits at the interface of analytic number theory and selected topics, viewed through the prism of Diophantine equations defining higher-dimensional algebraic varieties. A core part of the proposal involves using analytic methods (such as complex analysis, Fourier analysis and additive combinatorics) to tackle a range of problems about Diophantine equations. These include such
basic questions as precisely when families of equations admit integer or rational solutions and, furthermore, how ``dense'' these solutions are when they exist. In the reverse direction, a significant component of the proposal is dedicated to established problems in number theory (such as stable cohomology of moduli spaces and uniform spectral gaps for arithmetic lattices) which can be tackled via the successful analysis of intermediary Diophantine equations."
Max ERC Funding
801 187 €
Duration
Start date: 2012-12-01, End date: 2017-11-30
Project acronym INCORALS
Project Influence of nutrient starvation on corals' susceptibility to bleaching
Researcher (PI) Jorg Wiedenmann
Host Institution (HI) UNIVERSITY OF SOUTHAMPTON
Call Details Starting Grant (StG), LS8, ERC-2012-StG_20111109
Summary INCORALS will establish a novel conceptual model that introduces a transition of symbiotic algae from a nutrient limited to a nutrient starved state as a process that renders reef building corals more susceptible to heat stress. Elevated temperatures have been identified as the key driver for coral bleaching, which is the often fatal loss of corals’ symbiotic algae. Thus, studies have estimated that reefs will be lost within the next one hundred years as a result of global warming. High temperatures undoubtedly play a major role in triggering coral bleaching. However, observations made for instance during the 1998 bleaching event, suggest also a connection between the susceptibility of corals to heat stress and anthropogenically elevated nutrient levels. Here, I present evidence that unbalanced ratios of dissolved inorganic nitrogen to phosphorus in the water column perturb the lipid composition of photosynthetic membranes of zooxanthellae and result in an increased susceptibility to thermal bleaching. I have developed a novel conceptual model of coral bleaching that introduces nutrient starvation as a cause for increased heat stress susceptibility. The model clarifies the previously unexplained correlation between the reduction of the thermal bleaching threshold of corals and their exposure to coastal run-off with elevated concentrations of dissolved inorganic nitrogen. INCORALS will conduct an in-depth study of nutrient starvation of reef corals, comparing the impact of nitrogen, phosphorus and iron. INCORALS will combine physiological experiments under tightly controlled laboratory conditions and field-based studies, using a suite of optical methods and cutting-edge molecular techniques to study this yet unexplored cause of coral bleaching and define its relevance for coral ecosystems. The improved understanding of coral bleaching gained during this project is urgently required to develop knowledge-based management strategies to support coral reef resilience.
Summary
INCORALS will establish a novel conceptual model that introduces a transition of symbiotic algae from a nutrient limited to a nutrient starved state as a process that renders reef building corals more susceptible to heat stress. Elevated temperatures have been identified as the key driver for coral bleaching, which is the often fatal loss of corals’ symbiotic algae. Thus, studies have estimated that reefs will be lost within the next one hundred years as a result of global warming. High temperatures undoubtedly play a major role in triggering coral bleaching. However, observations made for instance during the 1998 bleaching event, suggest also a connection between the susceptibility of corals to heat stress and anthropogenically elevated nutrient levels. Here, I present evidence that unbalanced ratios of dissolved inorganic nitrogen to phosphorus in the water column perturb the lipid composition of photosynthetic membranes of zooxanthellae and result in an increased susceptibility to thermal bleaching. I have developed a novel conceptual model of coral bleaching that introduces nutrient starvation as a cause for increased heat stress susceptibility. The model clarifies the previously unexplained correlation between the reduction of the thermal bleaching threshold of corals and their exposure to coastal run-off with elevated concentrations of dissolved inorganic nitrogen. INCORALS will conduct an in-depth study of nutrient starvation of reef corals, comparing the impact of nitrogen, phosphorus and iron. INCORALS will combine physiological experiments under tightly controlled laboratory conditions and field-based studies, using a suite of optical methods and cutting-edge molecular techniques to study this yet unexplored cause of coral bleaching and define its relevance for coral ecosystems. The improved understanding of coral bleaching gained during this project is urgently required to develop knowledge-based management strategies to support coral reef resilience.
Max ERC Funding
1 285 671 €
Duration
Start date: 2012-11-01, End date: 2017-10-31
Project acronym JAWEVOL
Project The Origin of Jawed Vertebrates and the Evolution of Morphology in Deep Time
Researcher (PI) Martin Daniel Brazeau
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Call Details Starting Grant (StG), LS8, ERC-2012-StG_20111109
Summary Jawed vertebrates account for more than 99% of modern vertebrate diversity. Collectively, they comprise chondrichthyans (sharks, rays, and chimaeras) and osteichthyans (bony fishes and terrestrial vertebrates, including humans). The anatomy of jawed vertebrates includes a series of complex traits such as jaws, teeth, paired appendages, and novel skeletal tissues such as bone. In spite of the intensive investigation of jawed vertebrate evolution in comparative morphology and molecular developmental evolution, the origin and early diversification of this important group remains mysterious. This project seeks to inject a large body of fresh data into the problem of early jawed vertebrate origins and evolution and develop modernized tools for morphological phylogenetics. We will use an integration of expeditionary fieldwork, modern digital imaging technology, and newly developed numerical methods in phylogenetics to address the problems of early jawed vertebrate origins. The work will focus on the morphology and relationships of fossil jawed vertebrates from the Palaeozoic Era (approx. 540-250 million years ago) which exhibit the earliest evidence of jaws, teeth, and paired appendages. Fieldwork in Mongolia will deliver new taxonomic and morphological data from poorly explored regions and attack a major geographic bias in existing fossil archives. The project will exploit computed tomography scanning to analyze existing fossil archives of extract species. This work will provide a detailed scheme of phylogenetic relationships inferring the relationships of early fossil forms to modern jawed vertebrate lineages and document the evolutionary assembly of complex morphological traits of jawed vertebrates. These results will yield refined timelines for jawed vertebrate evolution that can help calibrate molecular clock studies and deliver a rich comparative framework for evolutionary morphological and developmental studies.
Summary
Jawed vertebrates account for more than 99% of modern vertebrate diversity. Collectively, they comprise chondrichthyans (sharks, rays, and chimaeras) and osteichthyans (bony fishes and terrestrial vertebrates, including humans). The anatomy of jawed vertebrates includes a series of complex traits such as jaws, teeth, paired appendages, and novel skeletal tissues such as bone. In spite of the intensive investigation of jawed vertebrate evolution in comparative morphology and molecular developmental evolution, the origin and early diversification of this important group remains mysterious. This project seeks to inject a large body of fresh data into the problem of early jawed vertebrate origins and evolution and develop modernized tools for morphological phylogenetics. We will use an integration of expeditionary fieldwork, modern digital imaging technology, and newly developed numerical methods in phylogenetics to address the problems of early jawed vertebrate origins. The work will focus on the morphology and relationships of fossil jawed vertebrates from the Palaeozoic Era (approx. 540-250 million years ago) which exhibit the earliest evidence of jaws, teeth, and paired appendages. Fieldwork in Mongolia will deliver new taxonomic and morphological data from poorly explored regions and attack a major geographic bias in existing fossil archives. The project will exploit computed tomography scanning to analyze existing fossil archives of extract species. This work will provide a detailed scheme of phylogenetic relationships inferring the relationships of early fossil forms to modern jawed vertebrate lineages and document the evolutionary assembly of complex morphological traits of jawed vertebrates. These results will yield refined timelines for jawed vertebrate evolution that can help calibrate molecular clock studies and deliver a rich comparative framework for evolutionary morphological and developmental studies.
Max ERC Funding
1 401 820 €
Duration
Start date: 2013-01-01, End date: 2018-12-31
Project acronym MOTZETA
Project Motivic zeta functions and the monodromy conjecture
Researcher (PI) Johannes Nicaise
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Call Details Starting Grant (StG), PE1, ERC-2012-StG_20111012
Summary The monodromy conjecture, formulated in the seventies by the Japanese mathematician Igusa, is one of the most important open problems in the theory of singularities. It predicts a remarkable connection between certain geometric and arithmetic invariants of a polynomial f with integer coefficients. The conjecture describes in a precise way how the singularities of the complex hypersurface defined by the equation f = 0 influence the asymptotic behaviour of the number of solutions of the congruence f = 0 modulo powers of a prime. Some special cases have been solved, but the general case remains wide open. A proof of the conjecture would unveil profound relations between several branches of mathematics.
In the past years, we have developed a new interpretation of the monodromy conjecture, based on non-archimedean geometry, and we have generalized it to a larger framework. A significant success of this approach was our proof of the monodromy conjecture for one-parameter degenerations of abelian varieties. The aim of our proposal is to generalize this proof to degenerations of Calabi-Yau varieties, and to adapt the arguments to the local case of the conjecture (hypersurface singularities). Degenerations of Calabi-Yau varieties play a central role in Mirror Symmetry, a mathematical theory in full development that emerged from string theory. We will explore in detail the connections between the monodromy conjecture and recent breakthroughs in Mirror Symmetry (tropical constructions of degenerating Calabi-Yau varieties). We hope to achieve these goals by combining advanced tools from several research domains, in particular: motivic integration, non-archimedean geometry, Hodge theory, logarithmic geometry and tropical geometry. We are convinced that all these research domains will greatly benefit from the systematic exploration of their mutual interactions, and that the impact of our project will go far beyond the monodromy conjecture.
Summary
The monodromy conjecture, formulated in the seventies by the Japanese mathematician Igusa, is one of the most important open problems in the theory of singularities. It predicts a remarkable connection between certain geometric and arithmetic invariants of a polynomial f with integer coefficients. The conjecture describes in a precise way how the singularities of the complex hypersurface defined by the equation f = 0 influence the asymptotic behaviour of the number of solutions of the congruence f = 0 modulo powers of a prime. Some special cases have been solved, but the general case remains wide open. A proof of the conjecture would unveil profound relations between several branches of mathematics.
In the past years, we have developed a new interpretation of the monodromy conjecture, based on non-archimedean geometry, and we have generalized it to a larger framework. A significant success of this approach was our proof of the monodromy conjecture for one-parameter degenerations of abelian varieties. The aim of our proposal is to generalize this proof to degenerations of Calabi-Yau varieties, and to adapt the arguments to the local case of the conjecture (hypersurface singularities). Degenerations of Calabi-Yau varieties play a central role in Mirror Symmetry, a mathematical theory in full development that emerged from string theory. We will explore in detail the connections between the monodromy conjecture and recent breakthroughs in Mirror Symmetry (tropical constructions of degenerating Calabi-Yau varieties). We hope to achieve these goals by combining advanced tools from several research domains, in particular: motivic integration, non-archimedean geometry, Hodge theory, logarithmic geometry and tropical geometry. We are convinced that all these research domains will greatly benefit from the systematic exploration of their mutual interactions, and that the impact of our project will go far beyond the monodromy conjecture.
Max ERC Funding
1 044 980 €
Duration
Start date: 2013-05-01, End date: 2018-04-30
Project acronym PolyInbreed
Project Coevolutionary Quantitative Genetics of Polyandry and Inbreeding in the Wild: New Theory and Test
Researcher (PI) Jane Margaret Reid
Host Institution (HI) THE UNIVERSITY COURT OF THE UNIVERSITY OF ABERDEEN
Call Details Starting Grant (StG), LS8, ERC-2012-StG_20111109
Summary A fundamental aim in biology is to understand the (co)evolutionary dynamics of the adaptive reproductive strategies that translate ecology into evolution. However, until now, it has not been possible to explicitly test key hypotheses explaining the evolution of major reproductive strategies in wild populations experiencing real-life ecological variation. I will revolutionise our understanding of the (co)evolution of two fundamental reproductive strategies, and our approach to achieving such understanding, by deriving entirely new evolutionary quantitative genetic theory and providing the first explicit tests of this theory in nature.
Genetic polyandry (female reproduction with multiple males) and inbreeding (reproduction among relatives) are fundamental reproductive strategies that profoundly influence the social, genetic and genomic structures of populations. Yet decades of research have failed to explain their (co)evolution and persistence in the face of sexually antagonistic selection. Current theory is inadequate because it does not consider ecology or coevolution or make critical quantitative predictions that permit definitive test of key hypotheses in wild populations. Key forces of direct and indirect selection on genetic variation underlying polyandry and inbreeding have consequently never been explicitly estimated.
I will derive new theory that defines the (co)evolution of polyandry and inbreeding in terms of sex-specific genetic (co)variances, thereby providing the conceptual advance required to drive a new generation of empirical test. I will estimate these genetic (co)variances through state-of-the-art quantitative genetic analysis of outstanding wild population data, thereby providing the first explicit tests of key hypotheses explaining the (co)evolution of polyandry and inbreeding in nature. I will thereby initiate and implement a new approach to understanding the evolution of reproductive strategies and answer long-standing questions in biology.
Summary
A fundamental aim in biology is to understand the (co)evolutionary dynamics of the adaptive reproductive strategies that translate ecology into evolution. However, until now, it has not been possible to explicitly test key hypotheses explaining the evolution of major reproductive strategies in wild populations experiencing real-life ecological variation. I will revolutionise our understanding of the (co)evolution of two fundamental reproductive strategies, and our approach to achieving such understanding, by deriving entirely new evolutionary quantitative genetic theory and providing the first explicit tests of this theory in nature.
Genetic polyandry (female reproduction with multiple males) and inbreeding (reproduction among relatives) are fundamental reproductive strategies that profoundly influence the social, genetic and genomic structures of populations. Yet decades of research have failed to explain their (co)evolution and persistence in the face of sexually antagonistic selection. Current theory is inadequate because it does not consider ecology or coevolution or make critical quantitative predictions that permit definitive test of key hypotheses in wild populations. Key forces of direct and indirect selection on genetic variation underlying polyandry and inbreeding have consequently never been explicitly estimated.
I will derive new theory that defines the (co)evolution of polyandry and inbreeding in terms of sex-specific genetic (co)variances, thereby providing the conceptual advance required to drive a new generation of empirical test. I will estimate these genetic (co)variances through state-of-the-art quantitative genetic analysis of outstanding wild population data, thereby providing the first explicit tests of key hypotheses explaining the (co)evolution of polyandry and inbreeding in nature. I will thereby initiate and implement a new approach to understanding the evolution of reproductive strategies and answer long-standing questions in biology.
Max ERC Funding
1 300 690 €
Duration
Start date: 2013-01-01, End date: 2017-12-31
Project acronym Redundancy
Project Functional redundancy of bacterial communities in the laboratory and in the wild
Researcher (PI) Thomas Bell
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Call Details Starting Grant (StG), LS8, ERC-2012-StG_20111109
Summary Understanding how species mediate ecosystem processes, such as energy and nutrient fluxes, is among the foremost challenges in ecology. Bacterial communities are pivotal for the functioning of the world’s ecosystems. Although there have been great advances in describing the biodiversity of bacteria, little effort has been directed at understanding how differences in bacterial communities translate into differences in ecosystem functioning. The proposed research will develop a comprehensive framework to determine how bacterial species affect functioning while in complex mixtures of species. Once this baseline is obtained, it is possible to ask detailed questions about the ‘functional ecology’ of bacterial communities. Foremost among these is whether ecological processes (species sorting) are more important than evolutionary processes (adaptation) in establishing species roles in ecosystems. The research has implications for the fundamental understanding how ecological communities operate.
Summary
Understanding how species mediate ecosystem processes, such as energy and nutrient fluxes, is among the foremost challenges in ecology. Bacterial communities are pivotal for the functioning of the world’s ecosystems. Although there have been great advances in describing the biodiversity of bacteria, little effort has been directed at understanding how differences in bacterial communities translate into differences in ecosystem functioning. The proposed research will develop a comprehensive framework to determine how bacterial species affect functioning while in complex mixtures of species. Once this baseline is obtained, it is possible to ask detailed questions about the ‘functional ecology’ of bacterial communities. Foremost among these is whether ecological processes (species sorting) are more important than evolutionary processes (adaptation) in establishing species roles in ecosystems. The research has implications for the fundamental understanding how ecological communities operate.
Max ERC Funding
1 484 258 €
Duration
Start date: 2013-02-01, End date: 2018-01-31
Project acronym RENAL CANCER
Project Analysis of the interplay between genetic mutation and altered cellular metabolism in renal neoplasia
Researcher (PI) Patrick John Pollard
Host Institution (HI) THE UNIVERSITY OF EDINBURGH
Call Details Starting Grant (StG), LS4, ERC-2012-StG_20111109
Summary Defining and characterising the defective genes in hereditary cancer syndromes has advanced our understanding of cellular function and disease mechanisms. Interestingly, some of these genes have been directly implicated in metabolic dysregulation, thus providing a link between genetic mutation and altered metabolism in cancer. One such syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC), is caused by germline mutations in the FH gene encoding the Krebs cycle enzyme fumarate hydratase. The aim of this proposal is to define pathways disrupted in HLRCC and within these to determine specific points, susceptible to genetic or chemical intervention, from which therapies might be derived to treat or prevent tumourigenesis. First, we will assess candidate mechanisms for FH-associated tumourigenesis which we have identified through recent studies, encompassing enzyme inhibition, protein modification, anti-oxidant signalling and altered energy metabolism. Secondly, to identify novel RCC associated mutations and clarify their relevance in the evolution and metabolism of RCC, transposon-based mutagenesis will be employed to induce RCCs in both wildtype and Fh1-deficient mice. Analyses will include histological analysis, metabolite profiling, and high resolution sequencing. Candidate genes will then be screened in relevant human RCC and pre-malignant lesions. Finally, a synthetic lethality screen will be performed in parallel with metabolic profiling to identify the pathways that are critical for the growth of FH-null cells. Taken together it is envisaged that this work will not only provide insights into this rare but aggressive disease but also inform on potential targets for intervention in more common cancers that are also characterised by metabolic dysregulation.
Summary
Defining and characterising the defective genes in hereditary cancer syndromes has advanced our understanding of cellular function and disease mechanisms. Interestingly, some of these genes have been directly implicated in metabolic dysregulation, thus providing a link between genetic mutation and altered metabolism in cancer. One such syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC), is caused by germline mutations in the FH gene encoding the Krebs cycle enzyme fumarate hydratase. The aim of this proposal is to define pathways disrupted in HLRCC and within these to determine specific points, susceptible to genetic or chemical intervention, from which therapies might be derived to treat or prevent tumourigenesis. First, we will assess candidate mechanisms for FH-associated tumourigenesis which we have identified through recent studies, encompassing enzyme inhibition, protein modification, anti-oxidant signalling and altered energy metabolism. Secondly, to identify novel RCC associated mutations and clarify their relevance in the evolution and metabolism of RCC, transposon-based mutagenesis will be employed to induce RCCs in both wildtype and Fh1-deficient mice. Analyses will include histological analysis, metabolite profiling, and high resolution sequencing. Candidate genes will then be screened in relevant human RCC and pre-malignant lesions. Finally, a synthetic lethality screen will be performed in parallel with metabolic profiling to identify the pathways that are critical for the growth of FH-null cells. Taken together it is envisaged that this work will not only provide insights into this rare but aggressive disease but also inform on potential targets for intervention in more common cancers that are also characterised by metabolic dysregulation.
Max ERC Funding
1 497 147 €
Duration
Start date: 2013-01-01, End date: 2017-12-31
Project acronym reversibleCOX
Project Reversibility and tissue specificity of mitochondrial translation defects in early childhood
Researcher (PI) Rita Horvath
Host Institution (HI) UNIVERSITY OF NEWCASTLE UPON TYNE
Call Details Starting Grant (StG), LS4, ERC-2012-StG_20111109
Summary We have recently identified the molecular genetic cause of a puzzling clinical syndrome, initially termed “benign infantile mitochondrial myopathy due to reversible cytochrome c oxidase (COX) deficiency”. While childhood-onset mitochondrial encephalomyopathies are usually severe, relentlessly progressive conditions with fatal outcome, this syndrome stands out by showing complete (or almost complete) spontaneous recovery. We have detected the homoplasmic m.14674T>C mutation in the mitochondrial mt-tRNAGlu gene in 17 affected individuals from 12 independent families of different ethnic origins. The m.14674T>C mutation affects the discriminator base of mt-tRNAGlu, the last base at the 3´-end of the molecule, where the amino acid via the terminal CCA is attached, therefore thought to impair mitochondrial translation, as reflected by the COX-negative fibres and the multiple respiratory chain defects in skeletal muscle. The spontaneous recovery of the patients suggests the existence of so far unknown cellular compensatory mechanisms.
We will investigate, i) why patients with reversible COX deficiency show an isolated muscle involvement, ii) why symptoms start uniformly in the first days or weeks of life, iii) what is the molecular basis of the age-dependent, spontaneous recovery, and iv) which factors influence mitochondrial protein synthesis in human cells, skeletal muscle and different tissues. We will study these factors in v) different types of mitochondrial disease.
From a scientific standpoint, this is one of the few hereditary conditions with a life-threatening onset showing recovery. Finding a clearly pathogenic homoplasmic mtDNA mutation offers a new paradigm of mtDNA pathogenesis, and studying this unique disease may unveil factors that are important in other mitochondrial disease. The long-term goal would be to upregulate or boost compensatory factors in patients with mitochondrial disease with the aim to open new avenues for therapy.
Summary
We have recently identified the molecular genetic cause of a puzzling clinical syndrome, initially termed “benign infantile mitochondrial myopathy due to reversible cytochrome c oxidase (COX) deficiency”. While childhood-onset mitochondrial encephalomyopathies are usually severe, relentlessly progressive conditions with fatal outcome, this syndrome stands out by showing complete (or almost complete) spontaneous recovery. We have detected the homoplasmic m.14674T>C mutation in the mitochondrial mt-tRNAGlu gene in 17 affected individuals from 12 independent families of different ethnic origins. The m.14674T>C mutation affects the discriminator base of mt-tRNAGlu, the last base at the 3´-end of the molecule, where the amino acid via the terminal CCA is attached, therefore thought to impair mitochondrial translation, as reflected by the COX-negative fibres and the multiple respiratory chain defects in skeletal muscle. The spontaneous recovery of the patients suggests the existence of so far unknown cellular compensatory mechanisms.
We will investigate, i) why patients with reversible COX deficiency show an isolated muscle involvement, ii) why symptoms start uniformly in the first days or weeks of life, iii) what is the molecular basis of the age-dependent, spontaneous recovery, and iv) which factors influence mitochondrial protein synthesis in human cells, skeletal muscle and different tissues. We will study these factors in v) different types of mitochondrial disease.
From a scientific standpoint, this is one of the few hereditary conditions with a life-threatening onset showing recovery. Finding a clearly pathogenic homoplasmic mtDNA mutation offers a new paradigm of mtDNA pathogenesis, and studying this unique disease may unveil factors that are important in other mitochondrial disease. The long-term goal would be to upregulate or boost compensatory factors in patients with mitochondrial disease with the aim to open new avenues for therapy.
Max ERC Funding
1 432 075 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym SOCODEV
Project Social development and life history evolution in cooperative mammals: an integrated approach
Researcher (PI) Michael Cant
Host Institution (HI) THE UNIVERSITY OF EXETER
Call Details Starting Grant (StG), LS8, ERC-2012-StG_20111109
Summary "Studies of cooperative animal societies have advanced understanding of social evolution but have also revealed great individual variation in cooperative behaviour and major life history traits, even among individuals of the same age, sex and social status. Research on laboratory mammals suggests that this variation may be explained by early life influences on development, but little is known about the function and mechanism of these developmental effects in wild mammals, or whether these effects are adaptive. We will address this shortfall in knowledge using both empirical and theoretical approaches. Our empirical work will use large-scale field experiments on a model cooperative mammal system, the banded mongoose Mungos mungo, to measure prenatal developmental impacts on offspring growth, care received, stress physiology, cooperation, health, cognition, aging and lifetime fitness. Our theoretical research will build on the recent economic theory of ‘skill formation’, and will generate new testable predictions about the coevolution of developmental responses and maternal and helper investment. The output of the research will be new insights into the evolutionary and proximate causes of individual variation in health, behaviour and life history in social mammals, and a new conceptual understanding of social development in cooperative organisms from insects to humans."
Summary
"Studies of cooperative animal societies have advanced understanding of social evolution but have also revealed great individual variation in cooperative behaviour and major life history traits, even among individuals of the same age, sex and social status. Research on laboratory mammals suggests that this variation may be explained by early life influences on development, but little is known about the function and mechanism of these developmental effects in wild mammals, or whether these effects are adaptive. We will address this shortfall in knowledge using both empirical and theoretical approaches. Our empirical work will use large-scale field experiments on a model cooperative mammal system, the banded mongoose Mungos mungo, to measure prenatal developmental impacts on offspring growth, care received, stress physiology, cooperation, health, cognition, aging and lifetime fitness. Our theoretical research will build on the recent economic theory of ‘skill formation’, and will generate new testable predictions about the coevolution of developmental responses and maternal and helper investment. The output of the research will be new insights into the evolutionary and proximate causes of individual variation in health, behaviour and life history in social mammals, and a new conceptual understanding of social development in cooperative organisms from insects to humans."
Max ERC Funding
1 493 322 €
Duration
Start date: 2013-01-01, End date: 2017-12-31
Project acronym SPGSV
Project Some Problems in Geometry of Shimura Varieties
Researcher (PI) Andrei Yafaev
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Call Details Starting Grant (StG), PE1, ERC-2012-StG_20111012
Summary "The Andre-Oort conjecture is an important problem in the theory of Shimura varieties. It also has significant applications in other areas of Number Theory, such as transcendence theory. The conjecture was proved assuming the Generalised Riemann Hypothesis by Klingler, Ullmo and Yafaev. Very recently, Jonathan Pila came up with a very promising strategy for proving the Andre-Oort conjecture unconditionally. The first main aim of this proposal is to combine Pila's ideas with the ideas of Klingler-Ullmo-Yafaev in order to obtain a proof of the Andre-Oort conjecture without the assumption of the GRH. We then propose to use these methods to attack the Zilber-Pink conjecture, a very vast generalisation of Andre-Oort. We also propose to consider several problems closely related to geometry of Shimura Varieties and the Andr\'e-Oort conjecture. Namely Coleman's cponjecture on finiteness of the number of Jacobians with complex multiplication for curves of large genus, the Mumford-Tate conjecture on Galois representations attached to abelian varieties over number field and Lang's conjecture on rational points on hyperbolic varieties in the context of Shimura varieties."
Summary
"The Andre-Oort conjecture is an important problem in the theory of Shimura varieties. It also has significant applications in other areas of Number Theory, such as transcendence theory. The conjecture was proved assuming the Generalised Riemann Hypothesis by Klingler, Ullmo and Yafaev. Very recently, Jonathan Pila came up with a very promising strategy for proving the Andre-Oort conjecture unconditionally. The first main aim of this proposal is to combine Pila's ideas with the ideas of Klingler-Ullmo-Yafaev in order to obtain a proof of the Andre-Oort conjecture without the assumption of the GRH. We then propose to use these methods to attack the Zilber-Pink conjecture, a very vast generalisation of Andre-Oort. We also propose to consider several problems closely related to geometry of Shimura Varieties and the Andr\'e-Oort conjecture. Namely Coleman's cponjecture on finiteness of the number of Jacobians with complex multiplication for curves of large genus, the Mumford-Tate conjecture on Galois representations attached to abelian varieties over number field and Lang's conjecture on rational points on hyperbolic varieties in the context of Shimura varieties."
Max ERC Funding
697 037 €
Duration
Start date: 2012-10-01, End date: 2017-09-30
Project acronym STATEMIG
Project Fitness drivers in long-distance migrants: the interacting roles of physiology, social biology, ecological and physical environments
Researcher (PI) Stuart Bearhop
Host Institution (HI) THE UNIVERSITY OF EXETER
Call Details Starting Grant (StG), LS8, ERC-2012-StG_20111109
Summary Long distance migration in birds is among the most dramatic and exciting phenomena in nature. However despite many years of study, there are still huge gaps in our understanding of how this behaviour shapes individual ecology and influences population processes. For example, we have very little understanding of how migratory animals manage trade offs within and among seasons and how these in turn drive variation in productivity, survival or breeding phenology. Increased understanding in this area has important implications for ecology, evolution conservation and management
Our lack of progress in this area is almost inevitable given the complex nature of migration. Migration is sequential in nature, meaning that an animal’s state in one season is heavily influenced by previous conditions. Therefore the costs/benefits of behaviours can be carried over into subsequent seasons and thus the processes regulating fitness may not occur at the time it is being expressed. This also means that regulating processes and response can also be separated spatially making it even harder to identify cause. These effects are likely to be emphasized in migrants because fuelling flights and breeding also places huge physiological demands on migratory birds. Yet few studies have linked the stress incurred during migration with subsequent fitness. Integrating mechanism and function would provide very important insights into the ecology and evolution of migration. In order to progress we need to able to follow large numbers of individuals throughout their annual cycles, tracking the different conditions they experience and how this influences their state at each point in time. I would use state of the art technologies and statistical tools to follow migratory geese throughout the year and integrate, for the first time, how interactions among physiological, social, ecological and climatic environments underpin state and in turn fitness across the annual cycle.
Summary
Long distance migration in birds is among the most dramatic and exciting phenomena in nature. However despite many years of study, there are still huge gaps in our understanding of how this behaviour shapes individual ecology and influences population processes. For example, we have very little understanding of how migratory animals manage trade offs within and among seasons and how these in turn drive variation in productivity, survival or breeding phenology. Increased understanding in this area has important implications for ecology, evolution conservation and management
Our lack of progress in this area is almost inevitable given the complex nature of migration. Migration is sequential in nature, meaning that an animal’s state in one season is heavily influenced by previous conditions. Therefore the costs/benefits of behaviours can be carried over into subsequent seasons and thus the processes regulating fitness may not occur at the time it is being expressed. This also means that regulating processes and response can also be separated spatially making it even harder to identify cause. These effects are likely to be emphasized in migrants because fuelling flights and breeding also places huge physiological demands on migratory birds. Yet few studies have linked the stress incurred during migration with subsequent fitness. Integrating mechanism and function would provide very important insights into the ecology and evolution of migration. In order to progress we need to able to follow large numbers of individuals throughout their annual cycles, tracking the different conditions they experience and how this influences their state at each point in time. I would use state of the art technologies and statistical tools to follow migratory geese throughout the year and integrate, for the first time, how interactions among physiological, social, ecological and climatic environments underpin state and in turn fitness across the annual cycle.
Max ERC Funding
1 499 224 €
Duration
Start date: 2013-02-01, End date: 2019-01-31
Project acronym TMHA
Project Transversal Multilinear Harmonic Analysis
Researcher (PI) Jonathan Bennett
Host Institution (HI) THE UNIVERSITY OF BIRMINGHAM
Call Details Starting Grant (StG), PE1, ERC-2012-StG_20111012
Summary This proposal consists of two intimately related programmes. The aim of Programme 1 is to make major contributions to the celebrated restriction theory for the Fourier transform and combinatorial problems of Kakeya-type using emerging multilinear techniques. The aim of Programme 2 is to develop a multilinear perspective on a much broader family of curvature-related problems in harmonic analysis, including important classes of Radon-like transforms that arise naturally in the theory of dispersive partial differential equations.
The specific objectives represent major challenges at the emerging frontiers of harmonic analysis with a variety of disciplines, including geometric analysis (encompassing heat-flow methods and convex geometry), affine geometry and algebraic topology.
Summary
This proposal consists of two intimately related programmes. The aim of Programme 1 is to make major contributions to the celebrated restriction theory for the Fourier transform and combinatorial problems of Kakeya-type using emerging multilinear techniques. The aim of Programme 2 is to develop a multilinear perspective on a much broader family of curvature-related problems in harmonic analysis, including important classes of Radon-like transforms that arise naturally in the theory of dispersive partial differential equations.
The specific objectives represent major challenges at the emerging frontiers of harmonic analysis with a variety of disciplines, including geometric analysis (encompassing heat-flow methods and convex geometry), affine geometry and algebraic topology.
Max ERC Funding
1 042 293 €
Duration
Start date: 2012-10-01, End date: 2018-09-30